This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00226-08v1 76/8/3502    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Bönquist, L. Articles by Sjöstedt, A. PubMed PubMed Citation Articles by Bönquist, L. Articles by Sjöstedt, A.

 Previous Article  |  Next Article 

Infection and Immunity, August 2008, p. 3502-3510, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00226-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

MglA and Igl Proteins Contribute to the Modulation of Francisella tularensis Live Vaccine Strain-Containing Phagosomes in Murine Macrophages

Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, Umeå SE-901 85, Sweden,¹ Department of Pediatrics, Division of Infectious Diseases, University of Washington, Seattle, Washington 98195²

Received 18 February 2008/ Returned for modification 13 March 2008/ Accepted 1 May 2008

The Francisella tularensis live vaccine strain (LVS), in contrast to its iglC mutant, replicates in the cytoplasm of macrophages. We studied the outcome of infection of the murine macrophagelike cell line J774A.1 with LVS and with iglC, iglD, and mglA mutants, the latter of which is deficient in a global regulator. Compared to LVS, all of the mutants showed impaired intracellular replication up to 72 h, and the number of the mglA mutant bacteria even decreased. Colocalization with LAMP-1 was significantly increased for all mutants compared to LVS, indicating an impaired ability to escape into the cytoplasm. A lysosomal acidity-dependent dye accumulated in approximately 40% of the vacuoles containing mutant bacteria but not at all in vacuoles containing LVS. Preactivation of the macrophages with gamma interferon inhibited the intracellular growth of all strains and significantly increased acidification of phagosomes containing the mutants, but it only slightly increased the LAMP-1 colocalization. The intracellular replication and phagosomal escape of the iglC and iglD mutants were restored by complementation in trans. In conclusion, the IglC, IglD, and MglA proteins each directly or indirectly critically contribute to the virulence of F. tularensis LVS, including its intracellular replication, cytoplasmic escape, and inhibition of acidification of the phagosomes.

Published ahead of print on 12 May 2008.

Editor: A. J. Bäumler